The majority of cases with isolated growth hormone deficiency (IGHD) are idiopathic (1). Monogenetic recessive inheritance of IGHD was shown to be caused by complete deletions of the GH-1 (IGHD IA)(2) and, more recently, by nonsense mutations of the GHRH receptor gene (3). Dominant transmission (IGHD II) was exclusively found in the presence of GH-1 splice site mutations which cause skipping of exon 3 (4,5). This in-frame deletion results in the loss of 40 amino acids and a presumably misfolded de132-71 GH. The prevalence of such mutations in families with IGHD II is high, up to 100% (6). The mechanism of the dominant negative effect of the mutant protein in only partly understood (7). In-vitro studies suggested cell-specific mechanisms in neuro-endocrine cells which included insufficient storage and secretion of the wild-type GH in the presence of the de132-71GH (8,9). Seven different splice site mutations in intron 3 of GH-1 have been reported (4,5,10–13). Because of the very compact gene structure of the GH-1, splicing is also affected by point mutations outside the conserved splicing sites (14). In addition, two GH-1 missense mutation (P89L and R183H) were recently implicated in IGHD II (15,16).